Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, especially in infants. Lung neutrophilia is a hallmark of RSV disease but the mechanism by which neutrophils are recruited and activated is unclear. Here, we investigate the innate immune signaling pathways underlying neutrophil recruitment and activation in RSV-infected mice. We show that MyD88/TRIF signaling is essential for lung neutrophil recruitment while MAVS signaling, leading to type I IFN production, is necessary for neutrophil activation. Consistent with that notion, administration of type I IFNs to the lungs of RSV-infected Mavs−/− mice partially activates lung neutrophils recruited via the MyD88/TRIF pathway. Conversely, lack of neutrophil recruitment to the lungs of RSV-infected Myd88/Trif−/− mice can be corrected by administration of chemoattractants and those neutrophils become fully activated. Interestingly, Myd88/Trif−/− mice did not have increased lung viral loads during RSV infection, suggesting that neutrophils are dispensable for viral control. Thus, two distinct pathogen sensing pathways collaborate for neutrophil recruitment and full activation during RSV infection

Chaos synchronization in the multi-feedback Ikeda model

We investigate synchronization between two unidirectionally coupled chaotic multi-feedback Ikeda systems and find both the existence and stability conditions for anticipating, lag, and complete synchronizations.Generalization of the approach to a wide class of nonlinear systems is also presented.Comment: 5 pages. submitte

Type I interferons and MAVS signaling are necessary for tissue resident memory CD8+ T cell responses to RSV infection

Respiratory syncytial virus (RSV) can cause bronchiolitis and viral pneumonia in young children and the elderly. Lack of vaccines and recurrence of RSV infection indicate the difficulty in eliciting protective memory immune responses. Tissue resident memory T cells (TRM) can confer protection from pathogen re-infection and, in human experimental RSV infection, the presence of lung CD8+ TRM cells correlates with a better outcome. However, the requirements for generating and maintaining lung TRM cells during RSV infection are not fully understood. Here, we use mouse models to assess the impact of innate immune response determinants in the generation and subsequent expansion of the TRM cell pool during RSV infection. We show that CD8+ TRM cells expand independently from systemic CD8+ T cells after RSV re-infection. Re-infected MAVS and MyD88/TRIF deficient mice, lacking key components involved in innate immune recognition of RSV and induction of type I interferons (IFN-α/β), display impaired expansion of CD8+ TRM cells and reduction in antigen specific production of granzyme B and IFN-γ. IFN-α treatment of MAVS deficient mice during primary RSV infection restored TRM cell expansion upon re-challenge but failed to recover TRM cell functionality. Our data reveal how innate immunity, including the axis controlling type I IFN induction, instructs and regulates CD8+ TRM cell responses to RSV infection, suggesting possible mechanisms for therapeutic intervention

Social Work in Modern Russia: Problems and Development Prospects

In the article are considered the questions connected with such as a social work. Нe article has the purpose to research the problems, inconsistencies and tendencies in understanding of regularities of different social help and support forms development.В статье рассматриваются вопросы, связанные со становлением и развитием социальной работы в нашей стране. Авторы делают попытку выявления проблем, противоречий и раскрытия некоторых тенденций развития различных форм социальной помощи и поддержки

РОЛЬ АДЪЮВАНТНОЙ ВНУТРИПУЗЫРНОЙ ХИМИОТЕРАПИИ В КОМБИНИРОВАННОМ ОРГАНОСОХРАНЯЮЩЕМ ЛЕЧЕНИИ НЕМЫШЕЧНО-ИНВАЗИВНОГО РАКА МОЧЕВОГО ПУЗЫРЯ

Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC) and to assess the results of its treatment using transurethral resection (TUR) as monotherapy and in combination with intravesical adjuvant chemotherapy (CT).Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.Цель исследования – повысить эффективность комбинированного лечения больных немышечно-инвазивным (НМИ) раком моче-вого пузыря (РМП). Оценить результаты лечения НМИ РМП при применении трансуретральной резекции (ТУР) в качестве монотерапии и в комбинации с внутрипузырной адъювантной химиотерапией (ХТ).Материалы и методы. Проведен анализ результатов лечения 59 пациентов с НМИ РМП. В 1-й группе (n = 22) больным была выполнена ТУР, во 2-й (n = 19) – ТУР и однократное внутрипузырное введение химиопрепарата, в 3-й (n = 18) выполнены ТУР и длительное применение внутрипузырной ХТ.Результаты и обсуждение. Частота рецидивов в 1-й группе составила 59,1 %, во 2-й – 57,9 %, в 3-й – 38,89 %. Установлено, что внутрипузырная ХТ в большей степени оказывает влияние на профилактику рецидива в зоне резекции. Частота данного рецидива в 1-й группе составила 31,81 %, во 2-й – 26,32 % и в 3-й – 5,56 %.Выводы. Адъювантная внутрипузырная ХТ является эффективным методом профилактики рецидивов РМП.